A RISK WORTH TAKING
Little Layla underwent gene therapy that had been tested only on mice – and she’s now free of leukaemia
THEY had a difficult choice to make – but for them it was a no-brainer. They had to choose between allowing their baby daughter to be given a first-of-its-kind medical treatment that had no guarantee of working or preparing to say goodbye to her.
Ashleigh Richards and Lisa Foley didn’t even consider not doing the experimental treatment. Despite the fact it had only ever been tested on mice, the couple from Enfield, London, weren’t ready to give up on their daughter, Layla (now 2), who had been diagnosed with acute lymphoblastic leukaemia at 14 weeks.
“It was scary to think the treatment had never been used in a human before but even with the risks there was no doubt we wanted to try it,” Ashleigh says. “Layla was sick and in lots of pain so we had to do something.”
The result of that decision is now making headlines around the globe as scientists realise the potential the technique of gene editing has to save millions of lives.
Doctors don’t claim to have found a cure but they’re describing it as a landmark in the use of new gene engineering technology. And even though there are questions around the ethics of what’s being dubbed “designer genes” it’s brought hope to millions of people in the same situation as Layla’s parents.
LAYLA was at death’s door in 2015 when a team of specialists from London’s Great Ormond Street Hospital and University College London contacted her parents. The little girl’s cancer was particularly aggressive and she was subjected to several rounds of chemotherapy – and when that didn’t work, the hunt was on for a suitable bone marrow donor.
Ashleigh, a driver, and Lisa, a dental receptionist, were thrilled when a match was found – but the treatment failed and the couple were told to prepare for the worst: their baby was dying.
Then came the news: there was a chance she could be saved with a new treatment – but it came with risks. Doctors explained there were no guarantees: this was brand-new territory and the chances it could fail were high.
“We just prayed it would work,” Ashleigh says.
Just weeks after the new treatment began, doctors started to see signs of recovery. And now, 20 months later, Layla is showing no sign of leukaemia and is a happy, healthy little girl.
So how did it work? It’s a complex scientific procedure in which the patient’s T-cells – which play an important role in the body’s immune system – are extracted and modified to kill cancerous cells. They’re then put back into the patient’s body. But people with leukaemia or those who’ve had several rounds of chemotherapy often don’t have enough healthy T-cells to do this procedure.
That’s what makes Layla’s case so
groundbreaking – doctors extracted T-cells from donors then edited them using molecular tools called Talens, which function like scissors, before putting them into Layla’s system.
Specific genes in the T-cells were cut in order to make them behave in two ways. Firstly, the cells – now called UCART19 cells – were designed to be invisible to the strong leukaemia drugs that would normally kill them. And secondly, they were reprogrammed so they wouldn’t be rejected by Layla’s body and would target and fight only leukaemia cells, not Layla’s normal, healthy ones.
The treatment was so experimental doctors needed permission not only from Layla’s parents but also from an emergency ethics committee.
Lisa says they were prepared to try anything to save their baby. “The day before her first birthday we were told there was nothing more doctors could do for her,” she says. “All they could advise was palliative care ( just providing pain relief) – they were at the stage where they had little left to offer. We didn’t want to accept palliative care and so we asked the doctors to try anything, even if it hadn’t been tried before.”
Waseem Qasim, a professor of cell and gene therapy and a consultant immunologist at Great Ormond Street Hospital, was cautiously optimistic. “The approach was looking incredibly successful in laboratory studies, and so when I heard there were no options left for treating this child’s disease, I thought, ‘Why don’t we use the new UCART19 cells?’ ”
Once it was approved by the ethics committee Layla was given a 1 ml infusion of genetically engineered cells. The whole procedure took only 10 minutes.
“Layla didn’t notice anything was going on and was bouncing around her cot all the way through,” Ashleigh says.
Then there was a nervous wait of about two weeks as doctors checked for an immune response, which usually comes in the form of a rash or fever. Layla did develop a rash but it wasn’t deemed serious because she seemed fine otherwise.
“We didn’t know she was going to be so well,” Lisa says. “We were preparing ourselves for her to be in intensive care and were constantly waiting to pull the emergency bell. It was terrifying because you think that if she hasn’t gone to intensive care then it’s not working. We couldn’t believe it was going so smoothly.”
Two months later Layla returned to hospital for a second bone marrow transplant Lisa and Ashleigh were prepared to try anything to save their daughter. to restore her immune system.
“We still don’t know what the future holds,” Ashleigh says. “She’ll have monthly bone marrow checks for now and might be on some medicines for the rest of her life. It’s always at the back of your mind. It’s not like chickenpox that clears away; this is constant. You always have doubts.”
DESPITE the cautious approach, excitement is bubbling within the medical profession.
“This is the first time human cells, engineered in this particular way, have been given back to a patient and that was a big step for us,” Professor Qasim told the BBC.
“Technology is moving fast and the ability to target specific regions of the genome has suddenly become much more efficient. We think this technology will be the next phase of treatments.”
He says Layla’s recovery could prove to be a landmark for gene engineering, and the success of this treatment demonstrates the possibilities of these tools.
“The technology itself has enormous potential to correct other conditions where cells are engineered and given back to patients or to provide new properties to cells that allow them to be used in a way we can only imagine at the moment.”
Admittedly more time is needed to see whether the therapy has cured the disease or simply slowed its progression, but that doesn’t take away from the achievements so far.
The technique has since also been used on a 15-month-old girl with the same form of cancer and she’s also reported to be in recovery. No more details about her have been released.
The treatment is still undergoing trials but initial results have been so encouraging there’s potential it could be engineered to treat a variety of life-threatening conditions.
“The only way we’ll find out if this is a cure is by waiting one or two years but even having got this far from where we were is a major, major step,” says Great Ormond Street’s Dr Paul Veys.
He describes Layla’s treatment as “almost like a miracle”.
The medical world – and Layla’s parents – are hoping he’s right.